POTENT BETA-LACTAM INHIBITORS OF HUMAN CYTOMEGALOVIRUS PROTEASE

A series of novel monobactam inhibitors of human cytomegalovirus (HCMV ) protease has been described that possess a heterocyclic thiomethyl s ide chain at C-4. Changes to the heterocycle did not significantly cha nge the inhibitory activity of these compounds in an enzymatic assay, although improvements in solubility and cell culture activity were not ed. A number of permutations between C-4 substitutions and N-1 derivat ives led to the identification of several beta-lactams with antiviral activity in a plaque reduction assay. N-methyl thiotetrazole-containin g compounds were found to be the most potent inhibitors in the enzymat ic assay.